Paternal fenvalerate exposure transgenerationally impairs cognition and hippocampus in female offspring

作者：Feng Zhan, Yecheng Wang, Liu Quan-mei, Meng-Juan Guo, Huimin Zhu, Chi Zhang, De‐Xiang Xu, Xiu‐Hong Meng · 发表于：Ecotoxicology and Environmental Safety · 年份：2021 · DOI：10.1016/j.ecoenv.2021.112565 · 被引用次数：11 · 研究领域：Pesticide Exposure and Toxicity、Carcinogens and Genotoxicity Assessment、Retinoids in leukemia and cellular processes

The impairments of maternal fenvalerate exposure have been well documented in previous study, but little was known about the effects of paternal fenvalerate exposure. The current study aimed to assess the effects of paternal fenvalerate exposure on spatial cognition and hippocampus across generations. Adult male mice (F0) were orally administered with fenvalerate (0, 2 or 20 mg/kg) for 5 weeks. F0 males were mated with untreated-females to generate F1 generation. F1 males were mated with F1 control females to generate F2 generation. For F1 and F2 adult offspring, spatial learning and memory were detected by Morris water maze. Results showed that spatial learning and memory were impaired in F1 females but not F1 males derived from F0 males exposed to 20 mg/kg FEN. Furthermore, significant impairment of spatial learning and memory were found in F2 females but not F2 males derived from F0 males exposed to 20 mg/kg FEN. As expected, histopathology showed that neural density in hippocampal CA3 region was reduced in F1 and F2 females but not F1 and F2 males derived from F0 males exposed to 20 mg/kg FEN. Mechanistically, hippocampal thyroid hormone receptor alpha1 (TRα1) was down-regulated in F1 and F2 females derived from F0 males exposed to 20 mg/kg FEN. Correspondingly, hippocampal brain-derived neurotrophic factor, tropomyosin receptor kinase B and p75 neurotrophin receptor, three downstream genes of TR signaling, were down-regulated in F1 and F2 females. Taken together, the pre...